The general objective of this project is to synthesize antagonists of the luteinizing hormone-releasing hormone (LH-RH) capable of preventing ovulation. Antagonists will be devised so that steric, conformational and electronic similarities to LH-RH will be preserved, in order to attain recognition by the pituitary hormone receptors, but lacking the features necessary to elicit the hormonal response. Antagonists resistant to enzymatic degradation will be prepared as a means of prolonging duration of action and devising orally active antiovulatory agents. The effect of these analogs on the release of LH and FSH will be determined by bioassays, as well as their ability to inhibit ovulation in intact animals. Hormone-receptor interaction in relation to Structure Activity Relationship will be evaluated by means of binding studies involving labeled hormone with cell receptors in pituitary cell-free preparations. The conformation of LH-RH in solution will be studied to provide information on the steric conformational and electronic requirements of the hormone-receptor interaction.